Addictive Substance Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Department of Anesthesiology & Pain Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Mol Pain. 2021 Jan-Dec;17:1744806921999924. doi: 10.1177/1744806921999924.
Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain.
Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain ( ≥ 1.858 × 10), the GWAS of PHN patients revealed that the rs4773840 SNP within the gene region was significantly associated with PHN in the trend model (nominal = 1.638 × 10). In the additional gene-based analysis, one gene, , was significantly associated with chronic pain in the trend model (adjusted = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models.
These results suggest that the gene and rs4773840 SNP within the gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.
人体双胞胎研究和其他研究表明,慢性疼痛的遗传性在 30%到 70%之间。我们旨在确定可能导致慢性疼痛易感性和药物疗效的潜在遗传变异。我们使用全基因组基因分型阵列进行了全基因组关联研究(GWAS),该阵列包含超过 700,000 个标记,涉及 191 名慢性疼痛患者和 89 名带状疱疹后神经痛(PHN)患者亚组,以及 282 名健康对照受试者,采用多种遗传模型进行分析,随后对相同表型进行了额外的基于基因和基于基因集的分析。我们还对治疗疼痛的药物疗效进行了 GWAS。
尽管没有一个单核苷酸多态性(SNP)被发现与慢性疼痛( ≥ 1.858 × 10)具有全基因组显著相关性,但 PHN 患者的 GWAS 显示,基因区域内的 rs4773840 SNP 在趋势模型中与 PHN 显著相关(名义 = 1.638 × 10)。在额外的基于基因的分析中,一个基因, ,在趋势模型中与慢性疼痛显著相关(调整后 = 0.03722)。在基因集分析中,几个基因集与慢性疼痛和 PHN 显著相关。在任何遗传模型中,没有 SNP 与任何类型药物的疗效显著相关。
这些结果表明, 基因和基因区域内的 rs4773840 SNP 可能分别与慢性疼痛和 PHN 的易感性相关。